HUTCHMED (China) Limited announced the first presentation of results from the ongoing SAVANNAH global Phase II trial at the upcoming International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (“WCLC”), taking place August 6-9 in Vienna, Austria. SAVANNAH is a global Phase II study of HUTCHMED and AstraZeneca's (LSE/?STO/?Nasdaq:?AZN) savolitinib in combination with AstraZeneca's TAGRISSO® (osimertinib) in epidermal growth factor receptor (“EGFR”)-mutated non-small cell lung cancer (“NSCLC”) patients with mesenchymal epithelial transition receptor (“MET”) driven tumors, following disease progression on treatment with TAGRISSO®. In addition to continuing TAGRISSO® treatment, patients received savolitinib 300mg once daily, 300mg twice daily, or 600mg once daily.

A total of 294 patients are enrolled in the study. The abstract presents results from an analysis of 193 efficacy evaluable patients who received savolitinib 300mg once daily plus TAGRISSO® 80mg once daily at data cut-off date of August 27, 2021. Qualifying MET aberrations are MET amplification as detected by FISH (MET copy number = 5 and/or MET: CEP signal ratio = 2 [FISH5+]) or MET overexpression as detected by IHC (3+ in = 50% tumor cells [IHC50+]).

Additional analysis using an exploratory, higher cut-off level of MET aberration are presented. The higher cut-off levels for MET aberration are MET copy number = 10 (FISH10+) and/or 3+ staining = 90% tumor cells (IHC90+). The prevalence of this higher cut-off levels of MET aberration was 34% of patients centrally tested for enrollment in this study.

Results showed a trend toward improved response rates with increasing level of MET aberration. Across all patients in this analysis, objective response rate (“ORR”) was 32% [95% confidence interval (“CI”): 26-39%], median duration of response (“DoR”) was 8.3 months [95% CI: 6.9-9.7 months], and median progression-free survival (“PFS”) was 5.3 months [95% CI: 4.2- 5.8 months]. These results are consistent with the previously presented results from the TATTON global exploratory study in over 220 EGFR mutation positive NSCLC patients with MET amplified tumors following progression after treatment with any EGFR TKI.

Among the SAVANNAH patients who met the criteria for higher cut-off levels of MET aberration (n=108), ORR was 49% [95% CI: 39-59%], median DoR was 9.3 months [95% CI: 7.6-10.6 months], and mPFS was 7.1 months [95% CI: 5.3-8.0 months]. The safety profile of savolitinib plus TAGRISSO® was consistent with the known profiles of the combination and each treatment alone. Findings based on the ongoing SAVANNAH study, and the previously presented TATTON Phase Ib/II study, supported the initiation of the SAFFRON global Phase III study in patients with EGFR-mutated, MET-driven, locally advanced or metastatic NSCLC whose disease progressed on first- or second-line treatment with TAGRISSO® as the most recent therapy.

Patients will be prospectively selected for the higher level of MET aberration. The SAFFRON study will evaluate the efficacy and safety of savolitinib in combination with TAGRISSO® compared to pemetrexed plus platinum doublet-chemotherapy, the current standard-of-care treatment in this setting. Approximately 324 patients are planned to be randomized.

If successful, the multi-regional clinical trial (“MRCT”) may support registration for this combination globally. Two registrational studies are ongoing in China in EGFR mutation positive NSCLC with MET aberrations: the SANOVO study in treatment naïve patients, and SACHI study in patients whose disease progressed following treatment with any EGFR tyrosine kinase inhibitor (“TKI”). Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.

More than a third of the world's lung cancer patients are in China. Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC. The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.

Approximately 10-25% of NSCLC patients in the U.S. and Europe and 30-40% of patients in Asia have EGFR-mutated NSCLC. These patients are particularly sensitive to treatment with an EGFR TKI which blocks the cell-signaling pathways that drive the growth of tumor cells. While an EGFR TKI can provide a durable survival benefit to most patients, the majority will ultimately develop resistance to their first-line treatment, underscoring a great unmet need to tackle acquired resistance in this patient population.

MET is a tyrosine kinase receptor. Aberration of MET (amplification or overexpression) is present in both treatment naïve patients as well as being one of the primary mechanisms of acquired resistance to EGFR TKIs for metastatic EGFR-mutated NSCLC. Approximately 2-3% of NSCLC patients have tumors with MET exon 14 skipping alterations, a targetable mutation in the MET gene.

Among patients who experience disease progression post-osimertinib treatment, approximately 15-50% present with MET aberration. The prevalence of MET amplification and overexpression may differ depending on the sample type, detection method and assay cut-off used.